In this revised application for a Mentored Patient-Oriented Research Career Development Award (K23), Dr. David Kimhy will pursue training and research in the cognitive and neurobiological mechanisms of stress regulation and psychosis in schizophrenia. The goals of the training and research plan are integrated around the hypothesis that cognitive coping strategies mediate the link between stress and psychotic symptoms during recovery from psychosis in schizophrenia. Under the sponsorship of Dr. Dolores Malaspina, the training plan capitalizes on the resources of NYSPI/Columbia University, combining formal coursework, direct supervision, and clinical research experience and training. The plan involves mentorship and didactic instruction in key areas including: 1) psychosis research in schizophrenia using of Experience Sampling Method (ESM), 2) clinical methodologies for assessment of stress-regulating systems, 3) data analysis using multilevel linear modeling, and 4) cognitive-behavior therapy for psychosis (CBTp). Current methodologies have limited ecological validity to establish causal links between momentary changes in stress and psychosis. Dr. Kimhy will study simultaneously the real-time physiological and psychological correlates of psychosis using ambulatory assessment of cardiac autonomic regulation (Heart Rate Variability;HRV) synchronized with data collected using Experience Sampling Method (ESM) with Palm handheld computers. The research plan involves simultaneous probing of momentary psychotic symptoms, subjective stress, HRV, and cognitive coping strategies. Assessments will be conducted before and after pharmacological and CBTp treatments of psychosis. This methodology translates basic science into use in real-time, real-world environments (in-vivo and in-situ), allowing for the assessment of psychosis as part of the ebb-and-flow of daily functioning. Understanding these interactions will advance our understanding of the mechanisms of recovery from psychosis in schizophrenia. The proposed training and research plan will provide Dr. Kimhy with the knowledge, training, and experience necessary to develop as an independent researcher focusing on the neurobiological and psychological mechanisms of stress regulation and psychosis in schizophrenia.